Classification, pathogenesis and molecular pathology of primary CNS lymphomas

Area of Science:

• Neuropathology
• Hematopathology
• Oncology

Background:

• Primary central nervous system lymphomas (PCNSL) lack reliable histopathologic classification schemes, hindering clinical relevance.
• Existing classification systems for nodal lymphomas are not suitable for PCNSL.
• The REAL Classification may simplify PCNSL subtyping, but its reliability and clinical significance require further evaluation.

Purpose of the Study:

• To highlight the significant challenges in the classification, pathogenesis, and molecular pathology of PCNSL.
• To underscore the need for improved diagnostic and pathogenetic understanding of PCNSL.

Main Methods:

• Review of existing histopathologic classification schemes (Kiel, Working Formulation, REAL Classification).
• Assessment of the current state of knowledge regarding PCNSL pathogenesis and molecular genetics.
• Comparison of PCNSL with neuroectodermal brain tumors and nodal lymphomas.

Main Results:

• Histopathologic classification of PCNSL remains problematic, with current schemes lacking reliability and clinical relevance.
• There is a scarcity of experimental data on PCNSL origin and development.
• Limited information exists on the type and frequency of oncogene and tumor suppressor gene mutations in PCNSL.

Conclusions:

• PCNSL present major clinico-pathologic problems compared to other tumors.
• There is a significant lack of histopathologic consensus and pathogenetic/molecular genetic information for PCNSL.
• Increased research is crucial given the rising incidence and clinical impact of PCNSL.